Transfection experiments have defined the contribution of several genes to breast tumor progression. Thrombospondin is an extracellular matrix component with multiple biological functions. We transfected a wild type and C-terminally truncated forms of thbs-1 cDNA into the MDA-MB-435 breast carcinoma cell line, and examined its in vivo and in vitro behavior. The wild-type thbs-1 transfectants produced smaller primary tumors in the mammary fat pads of nude mice, and fewer metastases than either control transfectants or a C-terminally trucated thbs-1 transfectant. Expression of the wild type thbs-1 was accompanied by inhibition of endothelial growth in vitro as well as reduced capillary densities in vivo, suggestive of an angiostatic function. Transfection of the c-erb-B-2 oncogene into MDA-MB-435 breast carcinoma cells, at levels comparable to those observed in human tumors, resulted in no significant change in primary tumor size, but a 2-5 fold increase in tumor metastatic potential. The erb-B-2 transfectants failed to exhibit increased in vitro growth, colonization or motility as compared to the control transfectants, but responded to its putative ligand, Heregulin, in motility assays.